Measles Vaccination in the Presence or Absence of Maternal Measles Antibody: Impact on Child Survival

Aaby, Péter; Martins, Cesário; Garly, May‐Lill; Andersen, Andreas; Fisker, Ane Bærent; Claësson, Mogens H.; Ravn, Henrik; Rodrigues, Amabélia; Whittle, Hilton; Benn, Christine Stabell

doi:10.1093/cid/ciu354

Cited by 80 publications

(78 citation statements)

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“…Infants given early MV in the presence of maternal antibody had a marked survival advantage that only became apparent after a booster dose of MV was given at 9 months of age (Aaby et al, 2014). Animal studies have shown that a previous viral infection may lower viral replication of a subsequent heterologous viral infections due to stimulation of T-cell cross reactivity (Selin et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival: A Review

et al. 2016

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BackgroundLive vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesised that revaccination in presence of prior immunity enhances beneficial NSEs.MethodsLiterature search for studies of revaccination and mortality.FindingsIn two randomised trials (RCTs), two doses versus one dose of MV reduced all-cause mortality by 63% (95% CI: 23–83%) from 9 to 18 months of age. In a quasi-experimental study two doses before and after 9 months compared with one dose of MV after 9 months of age reduced mortality by 59% (25–81%). BCG-revaccination significantly enhanced BCG's effect against overall child mortality in two RCTs. In a natural experiment study of OPV campaigns over a 13-year-period in Guinea-Bissau, each additional dose of OPV was associated with a 13% (4–21%) reduction in mortality rate. The beneficial NSEs of smallpox vaccination for survival increased significantly with the number of smallpox vaccination scars.InterpretationRevaccination with live vaccines led to substantial reductions in overall mortality. These findings challenge current understanding of vaccines and may explain the beneficial effects of campaigns with live vaccines.

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Section: Discussionmentioning

confidence: 99%

Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival: A Review

et al. 2016

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“…As randomization was stratified for maturity (≥37 weeks of gestation vs <37 weeks); all results were presented by maturity. As previous studies of nonspecific effects have emphasized children with atopic predisposition, and shown differential effects by sex and by maternal immunity, we prespecified analyses of the main outcome stratified by these subgroups, as well as by factors previously associated with the development of atopic diseases (Table ).…”

Section: Methodsmentioning

confidence: 99%

Neonatal BCG vaccination and atopic dermatitis before 13 months of age: A randomized clinical trial

Thøstesen

Kjærgaard

Pihl

et al. 2017

Allergy

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“…7 From this perspective, the ‘true’ effect of an intervention is the measured reduction in overall mortality/morbidity under a certain set of specified conditions in relation to other interventions affecting mortality. For example, the optimal effect of early MV at 4.5 months of age was obtained when children were primed with OPV0 (and BCG) in the first weeks of life (this study), did not receive NVAS,3 did not receive campaign-OPV before (this study), did not receive DTP after early MV3 and did receive MV in the presence of maternal antibodies 20. When altering these conditions, and other potential priming conditions that we do not know about yet, the ‘true’ effect is no longer observed.…”

Section: Discussionmentioning

confidence: 93%

Does oral polio vaccine have non-specific effects on all-cause mortality? Natural experiments within a randomised controlled trial of early measles vaccine

et al. 2016

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BackgroundBCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs). If an unplanned intervention with a vaccine (a natural experiment) modifies the estimated effect in a randomised controlled trial (RCT), this suggests NSEs. We used this approach to test NSEs of triple oral polio vaccine (OPV).MethodsDuring an RCT of 2 doses of MV at 4.5 and 9 months versus 1 dose of MV at 9 months of age, we experienced 2 natural experiments with OPV. We assessed whether these OPV experiments modified the effect of 2-dose MV in the MV trial.SettingMV RCT conducted in urban Guinea-Bissau 2003–2009.InterventionsNatural experiments with OPV due to missing vaccine and the implementation of OPV campaigns.Main outcome measureChanges in the mortality rate ratio (MRR) for 2-dose MV versus 1-dose MV.ResultsFirst, the MRR (2-dose/1-dose MV) overall was 0.70 (0.52 to 0.94), but the MRR was 1.04 (0.53 to 2.04) when OPV at birth (OPV0) was not given, suggesting that early priming with OPV was important for the effect of 2-dose MV. The effect of OPV0 depended on age of administration; the MRR (2-dose/1-dose MV) was 0.45 (0.29 to 0.71) for children receiving OPV0 in the first week of life, but 3.63 (0.87 to 15.2) for those receiving OPV0 after the first month of life (p=0.007, test of no interaction). Second, campaign-OPV may have reduced the difference between the randomisation groups since the MRR (2-dose/1-dose MV) was 0.60 (0.42 to 0.85) for children who had not received campaign-OPV before RCT-enrolment versus 0.72 (0.23 to 2.31) and 1.42 (0.70 to 2.90) for children who had received 1 or 2 doses of campaign-OPV-before-enrolment, respectively.ConclusionsBissau had no polio infection during this trial, so OPV0 and campaign-OPV may have NSEs since they modified the effect of 2-dose MV in an RCT. Different interventions may interact to a much larger effect than usually assumed.

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Measles Vaccination in the Presence or Absence of Maternal Measles Antibody: Impact on Child Survival

Abstract: In 2-dose trials, early measles vaccination at 4–6 months in presence of maternal measles antibody was associated with significantly better survival to age 5 years than vaccination in absence of measles antibody. Confounding factors did not explain the effect.

Cited by 80 publications

References 35 publications

Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival: A Review

Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival: A Review

Neonatal BCG vaccination and atopic dermatitis before 13 months of age: A randomized clinical trial

Does oral polio vaccine have non-specific effects on all-cause mortality? Natural experiments within a randomised controlled trial of early measles vaccine

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